While significant progress continues to be made, it is not likely that a safe and effective cure or vaccine for HIV will be developed soon. The success of these goals will depend on future HIV researchers, many of whom are likely to be trained in the next five to ten years. The goal of this K24 proposal is to provide the applicant with sufficiet support to mentor trainees in state-of-the-art translational and patient oriented HIV research and to expand his involvement in UCSD's wide array of training programs. This application is built upon funded, active and ongoing research projects, where the mentee is the primary leader and is trained in every aspect of study design, execution, analyses, results interpretation and publication. The presented studies provide opportunities for in-depth mentoring as well as investigation into important and open scientific questions in HIV pathogenesis. These goals will be met in the following three aims, which incorporate multiple clinical studies and six current mentees. SPECIFIC AIM 1: To determine virologic and immunologic dynamics during primary HIV infection by investigating: the genital tract (1A), gut associated lymphoid tissue (1B), and the neutralizing antibody response in the blood (1C). SPECIFIC AIM 2: To validate pooling methods for diagnostic purposes in resource limited settings to detect: virologic failure of antiretroviral therapy (2A) and sub-acute malaria infection in the setting of HIV infection (2B). SPECIFIC AIM 3: To use molecular epidemiologic methods to characterize HIV-1 transmission networks between San Diego and Tijuana. Taken together, this proposal will allow the mid-career applicant to continue and expand his HIV research and mentoring activities.